Biofabrication and in vivo evaluation of a hybrid osteochondral implant consisting of structurally organised engineered cartilage on a 3D-printed metal scaffold.

Abstract

Restoration of the osteochondral unit presents a substantial challenge due to the complex functional demands placed on cartilage and underlying subchondral bone, with each region requiring tailored approaches to ensure successful repair. This study describes a new biofabrication strategy to manufacture a hybrid osteochondral implant for biological joint resurfacing, consisting of structurally organised cartilage engineered on the surface of a 3D-printed titanium alloy scaffold. The biofabrication framework utilises phenotypically distinct bone marrow-derived mesenchymal stromal/stem cell (MSC)- and chondrocyte-based microtissues that are zonally patterned in an attempt to form an articular cartilage layer with a zonal composition and structure that mimics the native tissue. The metallic scaffold was designed with a porous architecture, which in pilot in vivo studies were shown to support tissue formation and osseointegration. Building on this initial work, we next used a co-culture of chondrocytes and MSCs to engineer hyaline cartilage microtissues resistant to calcification, while microtissues generated using only MSCs were used to generate hypertrophic cartilage designed to regenerate the cartilage-bone interface. Spatially patterning these microtissues onto the surface of the metallic lattice scaffold constrained and directed their subsequent growth, resulting in the in vitro development of hyaline cartilage with a biomimetic collagen network. Implantation of this hybrid osteochondral graft in a critically sized caprine osteochondral defect model revealed osseointegration challenges in some animals, potentially contributing to cartilage deterioration and negatively impacting overall joint regeneration. This study highlights that engineering zonally organised osteochondral implants in vitro does not necessarily guarantee their successful performance in vivo, and provides further insight into the multiple challenges that must be addressed to successfully promote synovial joint regeneration.